PMID- 12220490
OWN - NLM
STAT- MEDLINE
DCOM- 20030703
LR  - 20190916
IS  - 0969-2126 (Print)
IS  - 0969-2126 (Linking)
VI  - 10
IP  - 9
DP  - 2002 Sep
TI  - Crystal structure of the MuSK tyrosine kinase: insights into receptor 
      autoregulation.
PG  - 1187-96
AB  - Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed selectively 
      in skeletal muscle. During neuromuscular synapse formation, agrin released from 
      motor neurons stimulates MuSK autophosphorylation in the kinase activation loop 
      and in the juxtamembrane region, leading to clustering of acetylcholine 
      receptors. We have determined the crystal structure of the cytoplasmic domain of 
      unphosphorylated MuSK at 2.05 A resolution. The structure reveals an 
      autoinhibited kinase domain in which the activation loop obstructs ATP and 
      substrate binding. Steady-state kinetic analysis demonstrates that 
      autophosphorylation results in a 200-fold increase in k(cat) and a 10-fold 
      decrease in the K(m) for ATP. These studies provide a molecular basis for 
      understanding the regulation of MuSK catalytic activity and suggest that an 
      additional in vivo component may contribute to regulation via the juxtamembrane 
      region.
FAU - Till, Jeffrey H
AU  - Till JH
AD  - Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New 
      York university School of Medicine, New York, NY 10016, USA.
FAU - Becerra, Manuel
AU  - Becerra M
FAU - Watty, Anke
AU  - Watty A
FAU - Lu, Yun
AU  - Lu Y
FAU - Ma, Yuliang
AU  - Ma Y
FAU - Neubert, Thomas A
AU  - Neubert TA
FAU - Burden, Steven J
AU  - Burden SJ
FAU - Hubbard, Stevan R
AU  - Hubbard SR
LA  - eng
GR  - DK52916/DK/NIDDK NIH HHS/United States
GR  - RR14662/RR/NCRR NIH HHS/United States
GR  - NS36193/NS/NINDS NIH HHS/United States
GR  - R01 NS036193/NS/NINDS NIH HHS/United States
GR  - R01 NS036193-05/NS/NINDS NIH HHS/United States
GR  - NS41311/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Structure
JT  - Structure (London, England : 1993)
JID - 101087697
RN  - 0 (Receptors, Cholinergic)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (MuSK protein, rat)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - Kinetics
MH  - Mass Spectrometry
MH  - Models, Molecular
MH  - Phosphorylation
MH  - Protein Conformation
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/*chemistry/*metabolism
MH  - Receptors, Cholinergic/*chemistry/*metabolism
MH  - Static Electricity
MH  - Structure-Activity Relationship
EDAT- 2002/09/11 10:00
MHDA- 2003/07/04 05:00
CRDT- 2002/09/11 10:00
PHST- 2002/09/11 10:00 [pubmed]
PHST- 2003/07/04 05:00 [medline]
PHST- 2002/09/11 10:00 [entrez]
AID - S0969212602008146 [pii]
AID - 10.1016/s0969-2126(02)00814-6 [doi]
PST - ppublish
SO  - Structure. 2002 Sep;10(9):1187-96. doi: 10.1016/s0969-2126(02)00814-6.